Chapter 15.9: Drug detection and analysis Chapter 15.6: Environmental impact of some medications D.9: A variety of analytical techniques is used for detection, identification, isolation and analysis of medicines and drugs. D6: The synthesis, isolation, and administration of medicines can have an effect on the environment.

Drug isolation and purification  Isolation of drugs in pure form is important!  When synthesis is completed, how do we purify the drug?  By using and exploiting the different physical properties!  Differences in solubilities in different solvents  Like we saw with aspirin  Differences in volatility  Like we saw with aldehydes from primary alcohols

Organic structure and solubility  Solubility of a compound: like dissolves like  But more specifically, the intermolecular forces  Between molecules of the solvent and solute particularly  Aspirin is modified to be more aqueous so it more soluble  Fluoxetine (Prozac) is also modified  Extraction: choosing a solvent to selectively dissolve a particular component  Solvent extraction: using the solubility of a compound into a particular solvent and an immiscible one

Solvent extraction  A compound, X, is synthesized in an aqueous solution  It is known that X has greater solubility in non-polar solvents such as hexane  Hexane is less dense than water, so when poured together, hexane is the top layer  Shaking the mixture vigorously in a separation funnel will allow X to move into the hexane layer  Allowing the layers to separate and pouring out the bottom layer keeps the X and hexane layer  Evaporate the hexane to retain X  Separation Separation  Then recrystallization

Organic structure and volatility  IMFs also affect boiling point of a compound  Molecular size: larger molecules = more LDFs and higher boiling point  Polarity: more polar functional groups lower boiling point (H-bonds) Amide > carboxyl > hydroxyl > ketone > aldehyde > amino > ester > ether  Fractional distillation  Separation of the mixture of liquids within a narrow boiling point range into fractions We will be saving the fractional distillation equations and Raoult’s Law for next year when you work on chapters 6-7

Drug detection: steroids  Steroids: lipids with 4 fused rings (steroidal backbone)  Section 34 in Data Booklet  Cholesterol and sex hormones are commonly tested for steroids  Anabolic steroids (testosterone analogues)  Use of GC-MS (gas chromatography-mass spectrometry)  GC separates mixture into pure substances  MS identifies and quantifies components of mixture  GC: GC:  MS: MS:  GC-MS: GC-MS:  Fundamentals of GC: Fundamentals of GC:

GC-MS overview

Drug detection: ethanol  Roadside breathalyzers use K 2 Cr 2 O 7 crystals to determine the concentration of ethanol in the breath  The degree of change is determined by a photocell which can estimate the concentration (usu. used as a preliminary test)  Intoximeters are then used  Alcosensor uses a fuel cell to determine ethanol concentration  Fuel cells are discussed in chapter 9 (redox reactions)

Organic structure analysis & identification  Mass spectroscopy  Used to confirm the presence of a compound  Secondary peaks (other fragments) help to confirm compound structure  Impurities will appear as their specific peaks as well  Infrared spectroscopy  Functional groups show up as characteristic absorption peaks  Environment of the bond can influence other peaks  Can be used as a fingerprint of a particular compound  Proton NMR  Chemical shifts and number/height of peaks can help determine identify of compounds  Splitting pattern can help too  Impurities will show up as their own distinctive peaks

Mass spectroscopy

Infrared spectroscopy  Most spectra are compared to known compounds from a database Salicylic acidAspirin

Proton NMR

D.6: Environmental impact of some meds  Sustainable chemistry developed since 1991  12 principles (you do not need to learn these)  Address avoiding waste, maximizing production, and use of safe solvents  Reduce footprint and improve product and environmental safety

Solvent waste  Reactants left over from synthesis of a drug ~80% due to solvents/water  Solvent waste is the biggest contributor to emission of toxins into environment  Suitability of solvents is assessed by 3 factors:  Toxicity to workers: carcinogenic or other health issues  Safety of processing: flammable or toxic by-products  Harm to environment: contamination of water/soil, ozone depletion, release greenhouse gases when burned  Recycling solvents greatly reduces costs and emissions  Use of H 2 O or supercritical CO 2 whenever possible

Nuclear waste  More nuclear waste with growing nuclear technology  Two types of nuclear waste  Low-level waste: releases small amounts of ionizing radiation for a short time  Most medical nuclear waste is low-level  Clothing/shoe covers  Paper towels  Contaminated implements  Sealed in containers until safe, then disposed of normally  High-level waste: releases large amounts of ionizing radiation for a long time  Disposal problem = heat and radiation  Store in water 5-10 yrs before transfer to dry, shielded deeply buried structures  Green chemistry  Extract Uranium from incinerator ash  Use florescent dyes instead of radionuclides in diagnosis

Antibiotic waste  Overuse of antibiotics (especially broad-spectrum) has developed so- called superbugs  Can have resistance to multiple antibiotics  Methicillin-resistant Staphylococcus aureus (MRSA) is especially dangerous  Can occur in wound infections, pneumonia, blood poisoning  Mass production of antibiotics and release into environment is major cause of antibiotic resistance  Aquaculture and household pets  Growth promotion and prophylactic use in livestock  Especially bad as it can pass through animal and contaminate soil and water  Pest control in agriculture  Sanitizers in toiletries and cleaning products  Sterilization and culture selection in research and industry  Improper disposal of drugs

Obtaining the Tamiflu precursor: Green chemistry case study  Precursor of Tamiflu is shikimic acid or its salt shikimate  Most prevalent in Chinese star anise  Low yields are a problem esp. in 2005, so gov’ts stockpile it  Alternate sources are being sought  Fermentation of genetically engineered bacteria  Harvesting low yield precursor from pine needles  Extraction from suspension cultures of Indian sweetgum tree  Inexpensive, natural, no genetic engineering

Green Chemistry examples  Viagra  Uses modified reaction route = reduces by 75% amount of waste  Reduces solvent waste  Avoids use of toxic and hazardous reagents  Ibuprofen  Reduced steps in process from 6  3  Increased atom economy from 40-77%  Uses more of the material in final product  Decreased energy demand  Lyrica (Analgesic drug)  Uses a natural reagent of an enzyme  Water as solvent  Eliminated emissions of more than 3 million tons of CO 2 compared with original process  Cradle to grave